BACKGROUND/CONTEXT: Disc degeneration (DD) is a significant driver of low back pain and few treatments exist to treat the pain and disability associated with the disease. PURPOSE: Our group has developed a method to generate therapeutic discogenic cells as a potential treatment for symptomatic DD. These cells are derived and modified from adult nucleus pulposus cells. In this study, we evaluated the characteristics, mode of action, and in vivo efficacy and safety of these cells prior to human clinical testing. STUDY DESIGN: Privately funded in vitro studies and in vivo preclinical models were used in this study. METHODS: Discogenic cells generated from different adult human donors were evaluated for surface marker expression profile, matrix deposition and tumorigenic potential. Discogenic cells were then injected subcutaneously into nude mice to assess cell survival and possible extracellular matrix production in vivo. Finally, a rabbit model of DD was used to evaluate the therapeutic potential of discogenic cells after disc injury. RESULTS: We found that discogenic cells have a consistent surface marker profile, are multipotent for mesenchymal lineages, and produce extracellular matrix consisting of aggrecan, collagen 1 and collagen 2. Cells did not show abnormal karyotype after culturing and did not form tumor-like aggregates in soft agar. After subcutaneous implantation in a nude mouse model, the human discogenic cells were found to have generated regions rich with extracellular matrix over the course of 4 months, with no signs of tumorigenicity. Intradiscal injection of human discogenic cells in a rabbit model of DD caused an increase in disc height and improvement of tissue architecture relative to control discs or injection of vehicle alone (no cells) with no signs of toxicity. CONCLUSIONS: This study demonstrates that intradiscal injection of discogenic cells may be a viable treatment for human degenerative disc disease. The cells produce extracellular matrix that FDA device/drug status: Not applicable.
An epizootic of ulcerative to nodular ventral dermatitis was observed in a large breeding colony of 8-month to 5-year-old leopard geckos (Eublepharis macularius) of both sexes. Two representative mature male geckos were euthanized for diagnostic necropsy. The Chrysosporium anamorph of Nannizziopsis vriesii (CANV) was isolated from the skin lesions, and identification was confirmed by sequencing of the internal transcribed spacer region of the rRNA gene. Histopathology revealed multifocal to coalescing dermal and subcutaneous heterophilic granulomas that contained septate fungal hyphae. There was also multifocal epidermal hyperplasia with hyperkeratosis, and similar hyphae were present within the stratum corneum, occasionally with terminal chains of arthroconidia consistent with the CANV. In one case, there was focal extension of granulomatous inflammation into the underlying masseter muscle. This is the first report of dermatitis and cellulitis due to the CANV in leopard geckos.
This multi-institutional report describes 8 cases of rhabdomyosarcoma in horses. Four neoplasms were in the tongue and other areas of the mouth or head, 2 were in the abdominal wall, and 1 each was in right shoulder muscles and heart. Four rhabdomyosarcomas that were less than 10 cm in diameter were treated by surgical excision or radiation with no recurrence. Two neoplasms greater than 10 cm in diameter in the abdominal wall and the right shoulder were considered inoperable and led to decisions to euthanize the horses. Two neoplasms were incidental findings at necropsy. All the neoplasms were classified as embryonal except for 1 pleomorphic rhabdomyosarcoma. These 8 cases were evaluated with 9 published case reports of equine rhabdomyosarcoma. For all cases, the most common sites were limb muscles (5/17) and tongue (4/17). Metastasis was reported in 4 of the previously published cases; none was found in this study.
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